Parametric studies of selective D1 or D2 antagonists: effects on appetitive and feeding behaviour.

Dopamine receptor antagonists have long been known to suppress food intake. The main purpose of the present series of experiments was to investigate feeding in rats across several paradigms evaluating the effects of selective dopamine D1 and D2 antagonists. The selective D1 antagonist, SCH 23390, reduced FR8 operant responding for food (0.03mg/kg, s.c.) at a dose lower than that required to reduce food intake in two free-feeding situations (0.1mg/kg, s.c.). The selective D2 antagonist, YM 09151-2, had a biphasic effect on food intake in food-deprived rats, increasing food intake at a low dose (0.01mg/kg, i.p.), but decreasing intake at higher doses in deprived rats (0.1mg/kg, i.p.). A combination of subthreshold doses of SCH 23390 and YM 09151-2 resulted in a significant reduction in food intake. In nondeprived rats eating palatable food and in animals trained on an FR8 schedule of reinforcement, YM09151-2 exerted significant suppressant effects. The results suggest that the operant response is more sensitive to the effects of selective D1 and D2 antagonism than is the consummatory response. The findings also suggest a specific inhibitory role for dopamine D2 (and not D1) receptors on food intake, since selective D1 antagonism did not produce increases in food intake at any of the doses tested. This provides evidence that under some circumstances the effects of D1 and D2 receptor blockade are dissociable.